Fibroblast Growth Factor Receptor 3 (FGFR3) is a gene located on the short arm of chromosome 4 and a protein encoded by this gene is a receptor tyrosine kinase. This protein has a transmembrane domain in the central portion, a tyrosine kinase domain on the carboxyl-terminal, and an extracellular domain on the amino-terminal. FGFR3 is known to have isoforms including FGFR3b and FGFR3c resulting from alternative splicing conducted on the amino-terminal. FGF-1 and FGF-9 are ligands of FGFR3b, and FGF-1, FGF-2, FGF-4, FGF-8, FGF-9, FGF-17, FGF-18, and FGF-23 are ligands of FGFR3c. The protein is activated by auto-phosphorylation of its tyrosine residue through dimerization with another FGFR3 protein (Non-Patent Document 1 and Non-Patent Document 2).
It is known that in multiple osteosarcoma, FGFR3 is fused with an IgH gene by interchromosomal translocation, and an aberrant protein translated by the fusion gene results in abnormal proliferation of cells and achondroplasia (Non-Patent Document 3). Moreover, it is known that in peripheral T-cell malignant lymphoma, FGFR3 is fused with ETV6 by interchromosomal translocation (Non-Patent Document 4). Furthermore, it is known that in bladder cancer or the like, activating point mutation of the FGFR3 is observed. Furthermore, activating mutations of the FGFR3 are detected mainly in bladder cancer specimens. Introduction of these mutant genes into mouse normal cells, NIH3T3 cells, induces transformation of the NIH3T3 cells into malignant cells, whereas wild type FGFR3 does not induce the transformation in the same condition (Non-Patent Document 5).
Transforming, acidic coiled-coil containing protein 3 (TACC3) is a gene located on the short arm of chromosome 4, where FGFR3 is also located, and consists of 16 exons. It is known that TACC3 encodes a spindle motor protein which is involved in stabilization of mitotic spindle (Non-Patent Document 6).